151. Polyamidoamine (PAMAM) Dendrimers Modified with Cathepsin-B Cleavable Oligopeptides for Enhanced Gene Delivery
- Author
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Su Jeong Song, Tai Hwan Ha, Seulgi Lee, Sang Jae Son, and Joon Sig Choi
- Subjects
Materials science ,Polymers and Plastics ,Genetic enhancement ,cathepsin B ,arginine ,02 engineering and technology ,Gene delivery ,010402 general chemistry ,01 natural sciences ,gene delivery ,polyplex ,poly(amidoamine) dendrimer ,GFLG peptide ,histidine ,Article ,Cathepsin B ,HeLa ,lcsh:QD241-441 ,lcsh:Organic chemistry ,Cytotoxicity ,Cathepsin ,biology ,General Chemistry ,Transfection ,021001 nanoscience & nanotechnology ,biology.organism_classification ,0104 chemical sciences ,Biochemistry ,Nanocarriers ,0210 nano-technology - Abstract
Because of the complex mechanisms mediating cancer onset, prognosis, and metastatic behavior, different therapeutic approaches targeting these mechanisms have been investigated. Recent advancements in nanocarrier-based drug and gene delivery methods have encouraged scientific groups to investigate various novel therapeutic techniques. In this study, a poly(amidoamine) (PAMAM) polymer-based gene carrier containing the cathepsin B-enzyme sensitive sequence (glycine-phenylalanine-leucine-glycine, GFLG) was evaluated to determine transfection efficiency. Following the GFLG sequence, the surface of PAMAM generation 4 (G4) was conjugated with histidine (H) and arginine (R) for improved endosomal escape and cellular uptake, respectively. The successful synthesis of G4-GLFG-H-R was confirmed by H-1-nuclear magnetic resonance spectroscopy. The polyplex composed of G4-GLFG-H-R and pDNA was simulated by the enzyme cathepsin B and induced endosomal escape of pDNA, which was confirmed by gel electrophoresis. Compared with the G4 control, enzyme-sensitive G4-GLFG-H-R showed higher transfection efficiency and lower cytotoxicity in HeLa cells. These results demonstrated that G4-GLFG-H-R may be a highly potent and efficient carrier for gene therapy applications.
- Published
- 2017